Sarcolipin (SLN)

Sarcolipin is a small, **31-amino acid single-pass membrane protein** chiefly located in the **sarco/endoplasmic reticulum membranes of cardiac and skeletal muscle**[1][3][4][5]. It acts as a **regulatory subunit for the Ca²⁺-ATPase pump (SERCA)**, binding to SERCA and modulating its function by *reducing its apparent affinity for calcium* and by *uncoupling ATP hydrolysis from Ca²⁺ transport*. This “futile cycling” produces heat, making sarcolipin a key mediator of **muscle-based nonshivering thermogenesis**[3][5]. Its expression varies with tissue and species: in rodents, it is more abundant in the heart (especially atria), while in larger mammals (including humans), it is most highly expressed in fast-twitch skeletal muscle[4]. SLN is upregulated in heart failure and responds to β-adrenergic signaling, with implications in the regulation of contractility and metabolic rate. Structurally and functionally related to phospholamban, sarcolipin is notable both as a target and as a model for therapeutic manipulation of muscle energetic states and calcium homeostasis[2][3][4][5].

Other names

SarcolipinSLNMGC12301MGC125854MGC125855

Uncoupling inhibitor of SERCA (binds to SERCA and reduces calcium affinity while allowing ATP hydrolysis to continue without efficient Ca²⁺ transport, leading to heat generation via futile cycling); Phosphorylation state may regulate its interactions (possible reversal of inhibition via phosphorylation, but details are less clear and debated compared to phospholamban)